Fractyl Announces Presentation of Key Scientific Research at ADA 2018 Indicating That Modern Diets Durably Alter Duodenal Lining, Highlighting the Intestine’s Role in Type 2 Diabetes and NASH

Fractyl also announces one-year safety and efficacy data from the multicenter Revita-1 clinical trial of the Revita DMR system targeting the duodenal lining in patients with type 2 diabetes. In addition, Fractyl receives IDE approval from the FDA to initiate first U.S. clinical trial of Revita DMR in patients with type 2 diabetes.

LEXINGTON, Mass. and ORLANDO, Fla., June 23, 2018 /PRNewswire/ — Fractyl Laboratories Inc. (Fractyl) today announced the presentation of breakthrough research providing the first clear mechanistic link between modern diets and their causal effect on the pandemics of insulin resistance, obesity, and metabolic diseases. In an animal model, a modern diet high in fat and sugar caused overgrowth of the duodenal mucosa and overexpression of key gut hormones from the duodenum, the first segment of the intestine. These findings suggest a role of the duodenum in insulin resistance and metabolic diseases. The results also provide a rational explanation for the remarkable, weight-independent metabolic benefits of bariatric surgeries that bypass the duodenum. Fractyl will be presenting data supporting these findings with a poster (1900-P) entitled, “Westernized Diet-Induced Insulin Resistance in Mice Is Associated with Focal Duodenal Hyperplasia,” on Monday, June 25, from 12pm to 1pm EDT at the American Diabetes Association’s 78th Scientific Sessions (ADA 2018) in Orlando, Fla.

Fractyl’s lead product, Revita™ DMR, builds on these scientific observations and aims to reverse duodenal overgrowth with a minimally invasive intestinal procedural therapy targeting this root cause of metabolic diseases, such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD), which can progress to nonalcoholic steatohepatitis (NASH). At ADA, Fractyl’s collaborator will present full one-year clinical results from its single-arm, multicenter Revita-1 clinical trial, including device safety and durable effectiveness in this study of patients with poorly controlled type 2 diabetes. The study demonstrated significant and sustained reductions in HbA1c, insulin resistance, weight, and cardiovascular risk markers more than one year after a single procedure. Of particular interest, patients who also had evidence of NAFLD experienced statistically significant reductions of ALT from a baseline of 63 U/L to 41 U/L by six months and maintained at 41 U/L through one-year follow up, indicative of sustained benefit in their metabolic liver disease. The poster (1137-P) will be presented from 12pm to 1pm EDT on Sunday, June 24.

“I am impressed with the response of a single DMR treatment on metabolic health, including significantly lowering HbA1c levels by more than one percentage point one year after a single outpatient procedure, along with improvements in hepatic markers and weight loss,” said Ralph Defronzo, M.D., Professor of Medicine and Chief of Diabetes Division at the University of Texas Health Science Center and Deputy Director of the Texas Diabetes Institute, San Antonio, Texas. “This is consistent with our growing understanding of the key intestinal mechanism driving metabolic disease, which is not addressed easily with today’s therapies. The potential of being able to do so with a single procedure is promising and may offer a scientifically sound and convenient treatment alternative for type 2 diabetes and fatty liver disease.”

Building on the scientific and clinical evidence presented at ADA, Fractyl further announced that it has received an investigational device exemption (IDE) from the U.S. Food and Drug Administration (FDA) to initiate its first U.S. clinical trial of Revita DMR. In the European Union, the Revita DMR System previously received a CE mark and is currently being evaluated in a sham-controlled clinical trial conducted in multiple European and South American centers.

"Revita DMR is a minimally invasive procedure that builds on bariatric science and best practices in gastrointestinal endoscopy to offer a potential solution for many patients with type 2 diabetes and fatty liver disease,” said Steven A. Edmundowicz, M.D., Medical Director, Digestive Health Center, University of Colorado Hospital. “Given the substantial number of patients in our practices with these diseases and their tremendous unmet medical need, we are eagerly seeking safe and effective therapeutic options to help us restore the health of our patients.”

“Our clinical data to date indicate that Revita DMR offers the potential for unparalleled real world benefit for payers, physicians, and patients at high risk from the complications of metabolic diseases,” said Harith Rajagopalan, M.D., Ph.D., Cofounder and CEO of Fractyl. “We at Fractyl are motivated by the enthusiasm and support we have received by the clinical community worldwide, who see this as a potentially transformative approach to addressing the global epidemic of type 2 diabetes and fatty liver disease.”

About Fractyl and Revita™ DMR

Fractyl Laboratories is a private therapeutics company translating breakthrough insights in gut biology to develop disease-modifying interventions designed to restore health. Fractyl’s Revita DMR is a same-day minimally invasive therapeutic procedure that aims to treat two highly prevalent metabolic diseases, type 2 diabetes and NAFLD/NASH, and provide an important alternative to escalating T2D drug treatments. Currently, no therapies are approved to treat NAFLD/NASH. Revita DMR System received a CE mark for the treatment of Type 2 Diabetes in the European Union and an IDE exemption in the United States. The company plans to initiate its US clinical investigation of the Revita DMR System by the end of 2018. The Revita DMR System may be available for investigational use in other regions. Fractyl is headquartered in Lexington, Mass. For more information, visit www.fractyl.com, www.twitter.com/FractylLabs, or www.RevitaTrial.com.